The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

Gratwohl, Aloïs; Baldomero, Helen; Passweg, Jakob

doi:10.1007/s00277-015-2313-3

Cited by 17 publications

(7 citation statements)

References 66 publications

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“…Stem cell source did not predict late mortality, consistent with randomized trials [31,32] and some observational studies [33] of adult allogeneic HSCT recipients. Significant efforts are underway to optimize allograft regimens, identify the determinants and mechanisms of relapse, and develop risk-adapted protocols before and after transplantation [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

Vajdic

Mayson

Dodds

et al. 2016

Biology of Blood and Marrow Transplantation

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We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.

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Section: Discussionmentioning

confidence: 99%

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

Vajdic

Mayson

Dodds

et al. 2016

Biology of Blood and Marrow Transplantation

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“…Currently, HSCT-allo is the only treatment available that promotes a CML cure; however, morbidity and mortality rates related to this treatment are high, in addition to the difficulty of finding a donor, restricting its applicability [24][25][26][27]. Therefore, after the advent of ITK, HSCT-allo began to be used for CML treatment only in patients who developed therapeutic resistance [28].…”

Section: Discussionmentioning

confidence: 99%

MiR-125a-3p and MiR-320b Differentially Expressed in Patients with Chronic Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation and Imatinib Mesylate

Martins

Moraes

Cury

et al. 2021

IJMS

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Chronic myeloid leukemia (CML), a hematopoietic neoplasm arising from the fusion of BCR (breakpoint cluster region) gene on chromosome 22 to the ABL (Abelson leukemia virus) gene on chromosome 9 (BCR-ABL1 oncogene), originates from a small population of leukemic stem cells with extensive capacity for self-renewal and an inflammatory microenvironment. Currently, CML treatment is based on tyrosine kinase inhibitors (TKIs). However, allogeneic hematopoietic stem cell transplantation (HSCT-allo) is currently the only effective treatment of CML. The difficulty of finding a compatible donor and high rates of morbidity and mortality limit transplantation treatment. Despite the safety and efficacy of TKIs, patients can develop resistance. Thus, microRNAs (miRNAs) play a prominent role as biomarkers and post-transcriptional regulators of gene expression. The aim of this study was to analyze the miRNA profile in CML patients who achieved cytogenetic remission after treatment with both HSCT-allo and TKI. Expression analyses of the 758 miRNAs were performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatics tools were used for data analysis. We detected miRNA profiles using their possible target genes and target pathways. MiR-125a-3p stood out among the downregulated miRNAs, showing an interaction network with 52 target genes. MiR-320b was the only upregulated miRNA, with an interaction network of 26 genes. The results are expected to aid future studies of miRNAs, residual leukemic cells, and prognosis in CML.

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“…Until 2000, CML pharmacological regimens were limited to nonspecific drugs such as busulfan, hydroxyurea, and interferon-α (IFN-α) [ 97 ], which were complemented by BMT [ 98 ]. In 2001, the therapeutic landscape of CML changed dramatically when the FDA approved imatinib mesylate, an ATP-competitive TKI that potently inhibits BCR-ABL1 enzymatic activity [ 99 ].…”

Section: Gsk-3 Signaling In CMLmentioning

confidence: 99%

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Martelli

Paganelli

Evangelisti

et al. 2022

Cells

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Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.

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The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

Cited by 17 publications

References 66 publications

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

MiR-125a-3p and MiR-320b Differentially Expressed in Patients with Chronic Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation and Imatinib Mesylate

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

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